摘要
目的基于网络药理学的方法筛选补肺汤治疗慢性阻塞性肺疾病(COPD)的有效成分及作用靶点,探讨其相关机制。方法基于中药系统药理数据库与分析平台(TCMSP)分析既往文献中补肺汤组成中药(人参、黄芪、熟地黄、五味子、紫菀、桑白皮)的有效成分及其作用靶点。基于Gene Expression Omnibus(GEO)、Drugbank及Gene⁃cards数据库筛选COPD相关靶点,与补肺汤作用靶点取交集得到补肺汤治疗COPD的潜在基因,对潜在基因进行GO功能及KEGG信号通路富集分析。构建蛋白互作网络(PPI)图,采用拓扑分析的方法明确补肺汤治疗COPD的作用靶点。结果筛选后获得人参的有效成分40种、黄芪27种、熟地9种、五味子19种、紫菀22种、桑白皮36种;其中,槲皮素、黄芪异黄烷苷、山奈酚、异鼠李素、刺芒柄花素、β-谷甾醇、谷甾醇、原阿片碱、3,9-二甲氧基紫檀烷、7-甲基醚-青榆烯C为重要性排名前10位的有效成分。筛选得到有效成分的作用靶点141个,补肺汤治疗COPD的潜在基因1730个,取交集后共得到补肺汤治疗COPD的潜在靶点基因80个。补肺汤治疗COPD潜在基因的GO功能分析结果显示,主要涉及炎症反应、细胞凋亡、细胞增殖、氧化还原等方面;KEGG信号通路分析结果显示,主要涉及细胞衰老途径、丝裂原活化蛋白激酶(MAPK)信号通路、细胞周期循环途径、神经营养蛋白信号通路、细胞凋亡途径、Th17细胞分化途径、FoxO信号通路、PI3K/AKT信号通路、Rap1信号通路、Ras信号通路。PPI图筛选后的作用靶点包括丝裂原活化蛋白激酶1(MAPK1)、热休克蛋白90α家族A类成员1(HSP90AA1)、禽肉瘤病毒17的转化基因(JUN)等。结论补肺汤治疗COPD的有效成分是槲皮素、山奈酚等,可能通过作用于MAPK1、HSP90AA1、JUN等靶点调控细胞衰老途径、MAPK信号通路、细胞凋亡途径等而发挥治疗作用。
Objective To explore the effective ingredients and action targets of Bufei decoction in the treatment of chronic obstructive pulmonary disease(COPD)based on network pharmacology.Methods The active ingredients and action targets of Bufei decoction were analyzed in the previous literatures based on the Traditional Chinese Medicine Sys⁃tems Pharmacology Database and Analysis Platform(TCMSP).COPD-related targets were screened based on Gene Expres⁃sion Omnibus(GEO),Drugbank and Genecards databases,and were intersected with the targets of Bufei decoction to ob⁃tain the potential genes of Bufei decoction in treatment of COPD.GO function and KEGG signaling pathway enrichment analysis were performed on the potential genes.The protein-protein interaction(PPI)network diagram was established,and topological analysis was used to identify the action targets of Bufei decoction on COPD.Results The active ingredi⁃ents were 40 kinds in ginseng,27 kinds in Astragalus,9 kinds in Shudi,19 kinds in Schisandra chinensis,22 kinds in Aster,and 36 kinds in Morus alba;there were 141 action target.The top 10 most important active ingredients in the drugactive ingredient-target network included quercetin,astragalus isoflavanoside,and kaempferol,etc There were a total of 1730 COPD-related targets,of which 80 were the potential therapeutic targets of Bufei decoction for COPD.The GO func⁃tion analysis of the potential genes of Bufei decoction in treating COPD showed that it mainly involved inflammation,apop⁃tosis,cell proliferation,REDOX and so on.KEGG signaling pathway analysis results showed that it mainly involved cell senescence pathway,MAPK signaling pathway,cell cycle cycling pathway,neurotrophin signaling pathway,apoptosis pathway,Th17 cell differentiation pathway,FoxO signaling pathway,PI3K/AKT signaling pathway,Rap1 signaling path⁃way,and Ras signaling pathway.The core targets after PPI network screening included mitogen-activated protein kinase 1(MAPK1),heat shock protein 90αfamily class A member 1(HSP90AA1),and v-jun avian sarcona virus 17 oncogene ho⁃molog(JUN),etc.Conclusion The potential effective ingredients of Bufei decoction in treatment of COPD are querce⁃tin,kaempferol,etc.,which may play a role in regulating cellular senescence pathway,MAPK signaling pathway and apoptosis pathway by acting on MAPK1,HSP90AA1,JUN and other targets.
作者
焦玉洁
高智星
张晓谊
JIAO Yujie;GAO Zhixing;ZHANG Xiaoyi(Department of Respiratory and Critical Care Medicine,Urumqi Hospital of Traditional Chinese Medicine,Urumqi 830000,China)
出处
《山东医药》
CAS
2023年第23期29-33,共5页
Shandong Medical Journal
基金
新疆维吾尔自治区自然科学基金资助项目(2022D01A33)。
关键词
补肺汤
网络药理学
槲皮素
山奈酚
丝裂原活化蛋白激酶
慢性阻塞性肺疾病
Bufei decoction
network pharmacology
quercetin
kaempferol
mitogen-activated protein kinase 1
chronic obstructive pulmonary disease
作者简介
第一作者:焦玉洁(1984-),女,主治医师,主要研究方向为中西医结合治疗肺病。E-mail:372805634@qq.com;通信作者:张晓谊(1971-),女,主任医师,主要研究方向为中西医结合治疗肺病。E-mail:291190429@qq.com。
